Systematic Investigation of Multi-TLR Sensing Identifies Regulators of Sustained Gene Activation in Macrophages.

ABSTRACT: A typical pathogen presents a combination of Toll-like receptor (TLR) ligands during infection. Although individual TLR pathways have been well characterized, the nature of this "combinatorial code" in pathogen sensing remains unclear. Here, we conducted a comprehensive transcriptomic analysis of primary macrophages stimulated with all possible pairwise combinations of four different TLR ligands to understand the requirements, kinetics, and outcome of combined pathway engagement. We find that signal integration between TLR pathways leads to non-additive responses for a subset of immune mediators with sustained expression (>6 hr) properties and T cell polarizing function. To identify the underlying regulators, we conducted a focused RNAi screen and identified four genes-Helz2, Phf11d, Serta

SUBMITTER: Lin B 

PROVIDER: S-EPMC5584636 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature